The presence of a functional receptor is an absolute requirement for hormone action, and loss of a receptor produces essentially the same symptoms as loss of hormone. In addition to the receptor, there are fairly complex pathways involving numerous intracellular messengers and effector proteins. Accordingly, endocrine diseases can arise from abnormal expression or abnormal activity, or both, of any of these signal transduction pathway components. Finally, hormonal signals can be terminated in several ways, including hormone/receptor internalization, phosphorylation/ dephosphorylation, proteosomal destruction of receptor, and generation of feedback inhibitors.
Endocrinediseasescanbebroadlycategorizedashyperfunctionorhypofunctionofaspecifichormonalpathway.Hypofunctioncanbecausedbylackofactivehormoneorbyhormone resistance asaresultofinactivationofhormonereceptorsorpostreceptordefects.Testicular feminization syndrome isadramaticformofhormoneresistanceinwhichtheandrogenreceptorismutatedandcannotbeactivatedbyandrogens.Inpatientsinwhomthediagnosisisnotmadebeforepuberty,thetestisbecomeshyperstimulatedbecauseofabrogationofthenegativefeedbackbetweenthetestisandthepituitarygland.Theincreasedandrogenlevels 1.
Endocrine signaling involves (1) regulated secretion of an extracellular signaling molecule, called a hormone, into the extracellular fluid; (2) diffusion of the hormone into the vasculature and circulation throughout the body; and (3) diffusion of the hormone out of the vascular compartment into the extracellular space and binding to a specific receptor within cells of a target organ.
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The endocrine system is composed of the endocrine tissue of the pancreas, the parathyroid glands, the pituitary gland, the thyroid gland, the adrenal glands, and the gonads (testes or ovaries).
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Negative feedback represents an important control mechanism that confers stability on endocrine systems. Hormonal rhythms are imposed on negative feedback loops.
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Protein/peptide hormones are produced on ribosomes and stored in endocrine cells in membrane-bound secretory granules. They typically do not cross cell
Bae YJ, Kratzsch J. Corticosteroid-binding globulin: modulating mechanisms of bioavailability of cortisol and its clinical implications. Best Pract Res Clin Endocrinol Metab. 2015;29:761-772.
havenodirectbiologicaleffectasaresultofthereceptordefect.However,theandrogensareperipherallyconvertedtoestrogens.Thusaffectedindividualsaregeneticallymale(i.e.,46,XY)buthaveastronglyfeminizedexternalphenotype,afemalesexualidentity,andusuallyasexualpreferenceformen(i.e.,heterosexualinrelationtosexualidentity).Treatmentinvolvesremovalofthehyperstimulatedtestes(whichresideintheabdomenandposeariskforcancer),estrogenreplacementtherapy,andcounselingforthepatientand,ifoneexists,thepartner/spousetoaddressinfertilityandsocial/psychologicaldistress.
membranes readily and act through cell membrane– associated receptors.
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Catecholamines are synthesized in the cytosol and secretory granules and do not readily cross cell membranes. They act through cell membrane– associated receptors.
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Steroid hormones are not stored in tissues and generally cross cell membranes relatively readily. They act through intracellular receptors.
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Thyroid hormones are synthesized in follicular cells and stored in follicular colloid as thyroglobulin. They cross cell membranes and associate with nuclear receptors.
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Some hormones act through membrane receptors, and their responses are mediated by rapid intracellular signaling pathways.
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